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D-半乳糖、亚硝酸钠和三氯化铝联合作用对小鼠认知能力的影响

刘梅讯1，孙天敏2

目的探讨D-半乳糖、亚硝酸钠和三氯化铝联合作用对小鼠认知能力的影响。方法选取健康小鼠40只随机分为AD模型组、正常组，各20只。对模型组采用三氯化铝、D-半乳糖和亚硝酸钠联合给药，对正常组小鼠相应使用同体积生理盐水给药。均连续给药3个月，观察两组行为学、抗氧化指标和形态学染色的差异。结果①AD模型组的潜伏期、第一次穿越原平台位置的时间均明显长于正常组(P<0.01)，而在原平台象限的活动时间，前者又明显短于后者(P<0.01)；②AD模型组超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)活性明显降低、低于正常组(P<0.01)，而丙二醛(MDA)含量明显升高，高于正常组(P<0.01)；③刚果红染色，AD模型组海马CA2区细胞外可见多个Aβ斑，而正常组未见Aβ斑；④改良氨银染色，AD模型组海马CA2区可见锥体细胞稀少、不整齐，核周体内棕黑色细丝增粗、局部呈小块状，神经元外可见老年斑；而正常组海马CA2区组织结构清晰。结论通过D-半乳糖、亚硝酸钠和三氯化铝对小鼠的复合、慢性作用，部分复制了AD的病理变化，是建立AD动物模型比较理想的方法。

阿尔茨海默病；D-半乳糖；亚硝酸钠；三氯化铝；脂质过氧化；学习记忆

Abstract:ObjectiveTo investigate the effect of D-galactose， sodium nitrite，and alchlor on cognitive competence in mice.MethodsThe health mice were selected and divided into Alzheimer’s disease (AD) model group and normal group.Mice in model group were injected with alchlor， D-galactose and sodium nitrite for three consecutive months. Mice in normal group were injected with normal saline of the same volume. The behavior， anti-oxidative index and morphological staining pattern were observed.ResultsThe incubation period and the time when the original platform position passed through for the first time in AD model group were significantly longer than that in normal group (P<0.01).The activity time in the original platform position the former were significantly shorter in AD model group than that in normal group (P<0.01). The activities of SOD， GSH-Px decreased in AD model group，which was lower than that in normal group (P<0.01). MDA concentration rises in AD model group，which was higher than that in normal group (P<0.01). Congo red stainning method showed that many Aβ spots could be seen in hippocampal CA2 sector in AD model group， while no Aβ spot was observed in normal group. Improved amine silver staining method showed that few and irregular pyramidal cells could be found in hippocampal CA2 sector in AD model group. There was thickened black filament around the nucleus and it showed a forma of small patch in some area， and age pigment could be seen outside the neuron. However， the tissue structure of hippocampal CA2 sector of the normal group was clear.ConclusionAD pathological changes are partially modeled by the combined and chronic effect of D-galactose， sodium nitrite and alchlor in mice， which is proved to be an ideal method to establish AD animal model.

Keywords：Alzheimer’s disease；D-galactose;sodium nitrite；alchlor;lipid peroxidation；learning and memory

老年性痴呆又称阿尔茨海默病(Alzheimer’s disease，AD)，由德国医生Alois Alzheimer于1906年最先描述，是与年龄高度相关的、以进行性认知障碍为主要表现的中枢神经系统退行性疾病。AD脑三大病理变化为：神经元外由β-淀粉样蛋白(amyloid β-protein，Aβ)组成的老年斑(senile plaques，SP)、神经元内由异常磷酸化tau蛋白(p-tau)组成的神经元纤维丝缠结(neurofibrillary tangles，NFTs)以及神经元及其突触的广泛丢失。但其发病机制尚未完全明了，亦无根治药物。关于AD研究的最大难题是没有特异性的动物模型，以致于严重影响研究的针对性和实用性[1]。因而，探索建立理想的动物模型是目前AD研究最迫切的工作。现有的AD动物模型如老化型、损伤型、转基因型、胰岛素抵抗型、脑缺血型等，均只是在一个局部或一个点反映AD的病理变化和发病机制，急需建立AD复合模型，来揭示AD发病机制、提供研究以及指导治疗[1-3]。为此，本课题探讨D-半乳糖、亚硝酸钠和三氯化铝联合作用对小鼠认知能力的影响，试图为复制AD动物复合模型提供实验数据。……